2015 New Investigator Research Grant

Background
The tau protein helps maintain cell structure and facilitates the transport of nutrients in healthy nerve cells. However, in the brains of individuals with Alzheimer’s disease, tau proteins become abnormally modified and clump together forming tau tangles, one of the characteristic features of the disease. Tau tangles can be toxic to nerve cells and may contribute to nerve cell death in Alzheimer’s disease.

Research Plan
Dr. Herskowitz and colleagues have proposed studies to investigate if tau becomes abnormally modified early in the progression of Alzheimer’s disease, before significant brain damage has occurred. If tau becomes abnormal and accumulates into tangles before nerve cell death, drug treatments that inhibit this process may be able to halt or reverse the disease.

To investigate this question, Dr. Herskowitz’s team will use mice that have been genetically altered to have an Alzheimer’s-like condition. The researchers will treat the mice with a drug called fasudil, which can prevent the abnormal modifications of tau protein that can lead to the formation of tangles. They will determine if fasudil treatment can prevent tau clumping in nerve cells and improve the animals’ brain function. Dr. Herskowitz and colleagues will also examine brain tissue from people who had Alzheimer’s disease or mild cognitive impairment (a condition of cognitive decline which often precedes Alzheimer’s) to see where abnormal modifications of the tau protein are most likely to occur in the human brain.

Impact
The results of these studies will improve our understanding of how abnormal tau contributes to brain changes associated with Alzheimer’s disease. If successful, the findings related to fasudil treatment have the potential to move this drug into clinical trials for Alzheimer’s disease.